The invention relates to a process for forming bioresorbable rods, pins, screws made of resorbable polymeric material such as polylactides and polyglycolides. More particularly, it relates to a continuous process for forming a rod, strip, tape or bar, which continuous rod, strip, tape or bar is cut into segments so that resorbable meshes, plates, pins, medullary rods, and screws maybe manufactured therefrom.
Various processes have been proposed to form bioresorbable or bioabsorbable thermoplastic rods, pins, screws and plates for use in orthopedics. These processes are either xe2x80x9cbatchxe2x80x9d or continuous xe2x80x9cprocessesxe2x80x9d. A batch process is performed on preformed molded bodies whereas a continuous process makes strips, tape, bar or rods in a continuous manner. Continuous processes were first used to manufacture resorbable sutures. Such processes such as melt-processing or spinning are taught in U.S. Pat. Nos. 3,636,956 and 3,797,499. Melt-processing consists of melting in an extruder and extruding the material as a filament and then stretching the filament for orientation of the polymer chains. Melt-spinning is a term of art describing this process where absorbable sutures made of copolymers of L-lactide and/or glycolide are continuously extruded to form suture filaments which were then drawn at temperatures of between 50xc2x0 C. and 140xc2x0 C. at draw ratios up to 11 and then annealed.
U.S. Pat. Nos. 3,463,158 and 3,739,773 also relate to continuous processes for forming absorbable implants made of polyglycolic acid. As in U.S. Pat. Nos. 3,636,956 and 3,797,499, a melt spinning process is used to form filaments which are then drawn at about 55xc2x0 C. to five times their original length. The diameter of these filaments may easily be increased to form self-supporting members or rods.
A continuous process for forming rods is also shown in European Patent Application EP 0 321 176 A2. This patent application relates to a continuous process and as shown in FIG. 4 thereof, a polylactic acid rod is continuously extruded and cooled and then drawn at a temperature above its glass transition temperature with tension being maintained on the polymer rod during cooling.
Various patents relate to a batch process in which a rod or bar is formed by molding, such as injection molding, and then later drawn to orient the polymer chains and strengthen the article. Such a process is disclosed in Ikada et al. patent 4,898,186, in which a poly-L-lactide shaped body is formed in a mold and is then axially drawn about 2 to 10 times at a temperature of 70xc2x0 C. to about 120xc2x0 C. Ikada et al. U.S. Pat. No. 5,227,412 also relates to a batch method in which molded articles are oriented after molding. A similar process is taught in Tormala et al. U.S. Pat. No. 4,968,317 in which poly-L-lactide rods are made by injection molding and then drawn at a draw ratio of 7 at temperatures up to 40xc2x0 below the melting point of the polymer. All of the processes taught by the batch method patents suffer from low production rates, since each molded rod is individually heated and then drawn to orient the molecular chains.
It has been found that the continuous process of forming bioabsorbable rods, strips or tapes, while more productive than the molded process, was difficult to implement because the cross-section of the extrusion was difficult to control. This is the result of the extrusion process in which polymer granules are fed from a hopper into an extruder where they are heated and melted and then extruded usually by a screw. The flow rate from the hopper into the melting area of the extruder and then into the screw, which extrudes the material, is not constant for a variety of reasons, including that the weight of material in the hopper varies as material is withdrawn therefrom. This results in an extrusion having a non-uniform cross-section exiting the extruder and if a die is used to shape the extrusion, in turn, results in the extrusion leaving the die with a non-uniform cross-section.
As discussed below, because the extrusion is placed under a high tension during stretching or orientation, any non-uniformity in cross-section results in high stress areas within the extruded rod or strip which may result in the rod or strip breaking. Once the strip or rod extrusion breaks, the entire process must be stopped and many feet of expensive extrudate and time are wasted and these must be removed from the process line.
The process of the present invention solves this problem by placing a metering pump downstream of the extruder but prior to the die area. The metering pump has pressure transducers set to maintain the pressure into the pump and into the die area at constant predetermined pressure. By controlling the speed of the extruder screw sufficient material enters the metering pump and the die from the extruder. Laser micrometers downstream of the die are utilized to confirm that the cross-section is constant. The metering pump controls the speed of the extruder to maintain pre-set pressures at the pump input. Pressures are maintained by pressure transducers which send electrical signals to the controller unit of the pump which in turn controls the speed of the extruder. The laser micrometers may also be placed in a feedback loop to control the constancy of the rod or plate cross-section.
It is an object of the invention to provide a continuous process for forming bioresorbable plates, rods or bars having a constant cross-section and high strength and which retain their strength for a sufficient time after implantation for the intended use.
It is also an object of the invention to provide a continuous extrusion process for forming oriented thermoplastic extrusions of constant cross-section which can be cut into segments that may then be machined into screws, pins and plates for use as resorbable orthopedic implantable devices.
It is a further object of the invention to provide a continuous process for forming thermoplastic extrusions which extrudate can have its polymer chains oriented by stretching in a continuous process.
It is yet an additional object to provide a process for continuously forming bioabsorbable rods, strip, tape or bars made of a novel terpolymer of L-lactide, D-lactide and glycolide.
These and other objects of the present invention are accomplished by a process for forming an extrudate, such as a rod or strip of bioabsorbable polymeric material which includes continuously extruding thermoplastic material at a temperature above its melting point (normally between 125xc2x0 C. and 250xc2x0 C.) to form continuous rods, strips, tapes or bars having a tightly controlled cross-section. For polylactide, this temperature is preferably between 180xc2x0 C. and 200xc2x0 C. The extrusion takes place at rate of between 0.4 and 20 feet per minute. Once extruded, the extrudate enters a metering pump, which precisely controls the amount of material entering a die which shapes the extrudate. The die reduces the cross-section to a desired shape and consolidates the material. The extrudate is then cooled around its outer surface to form a skin such as by circumferentially blowing air around its outer skin. The extrudate is then passed through the cooling bath to cause nucleation. The cooling bath has a temperature of between 10xc2x0 C. and 50xc2x0 C. and may be composed of water or other liquid which does not react with the polymeric material being used.
The extrudate is then passed through a first puller downstream of the die with the first puller running at approximately the same speed as the extruder. The continuous extrudate then engages a second puller which is moving faster than the first puller so that the continuous extrudate is placed under tension. Intermediate the first and second pullers, the continuous extrudate is heated to a temperature above its glass transition temperature but below its melting point, which depending on the polymer, is between about 55xc2x0 C. and about 200xc2x0 C. and preferably between about 70xc2x0 C. and about 200xc2x0 C. and more preferably between about 70xc2x0 C. and about 100xc2x0 C. in an orientation bath or oven. The melting point of polylactide is around 200xc2x0 C. but the melting point of the novel terpolymer is about 140xc2x0 C. During orientation the temperature is kept above the glass transition temperature and preferably well below the melting temperature. The bath is preferably filled with boiling water at 100xc2x0 C. or in an air oven such as an infrared oven. The polymer is oriented by elongation while heated by stretching or drawing the extrudate between the first and second pullers at an elongation ratio of between 2:1 and 12:1. After the extrudate is elongated, the continuous extrudate is then annealed, either at the end of the same bath or oven where it is heated for orientation or in a separate heating bath or oven at a temperature of between about 65xc2x0 C. and about 110xc2x0 C. and preferably between 70xc2x0 C. and 100xc2x0 C. Tension is maintained on the extrudate during annealing by locating the second puller downstream of the annealing station. Once the continuous extrudate passes downstream of the second puller, tension is completely released before the extrudate cools to ambient temperature of about 25xc2x0 C. The extrudate then is continuously cut into sections of predetermined length for further processing such as into screws or pins.
Prior to extruding the thermoplastic raw material, which may be polyorthoesters, tyrosine derivatives, polydioxanone, trimethyl carbonate and alpha hydroxy polyesters such as L-lactide, D-lactide, copolymers of lactide (D-lactide, L-lactide or D/L-lactide) and glycolide or a terpolymer of L-lactide, D-lactide and glycolide or poly-4-hydroxy alkanaotes. One or more of these materials are placed in a hopper in granular form under an inert atmosphere such as a nitrogen, helium or argon atmosphere. Suitable lactides are disclosed in applicant""s U.S. Pat. Nos. 4,539,981 and 4,550,449 the teachings of which are incorporated herein by reference. A novel terpolymer of L-lactide, D-lactide and glycolide is disclosed in applicant""s co-pending application Ser. No. 09/263,268, filed Mar. 5, 1999, now U.S. Pat. No. 6,206,883, the teaching of which is incorporated herein by reference. Other polymers are alpha-hydroxy-alpha-ethylbutyric acid; alpha-hydroxy-beta-methylvaleric acid; alpha-hydroxyacetic acid; alpha-hydroxybutyric acid; alpha-hydroxycaporic acid; alpha-hydroxydecanoic acid; alpha-hydroxyheptanoic acid; alpha-hydroxyisobutyric acid; alpha-hydroxyisocaproic acid; alpha-hydroxyisovaleric acid; alpha-hydroxymyristic acid; alpha-hydroxyoctanoic acid; alpha-hydroxystearic acid; alpha-hydroxyvaleric acid; beta-butyrolactone; beta-propiolactide; gamma-butyrolactone; pivalolactone; or tetramethylglycolide or combinations thereof.
During orientation, the heating of the continuous extrudate is carried out in an oven containing either heated air or heated water at a temperature of about 100xc2x0 C. After orientation by stretching, the extrudate is allowed to anneal for a predetermined time in an air or in a water bath at a temperature of between about 65xc2x0 C. to about 100xc2x0 C. and preferably closer to 90xc2x0 C. The annealing can take place in the same oven or bath as the elongation, since the elongation may take place in the first part (first 12 inches) of the orientation oven depending on the process parameters. Total elongation in the first inches of the bath results in longer annealing time but results in a less uniform elongation from surface to core wherein elongation over several feet results in a more uniform elongation throughout the cross-section of the extrudate.
The process takes places in a continuous production line where the continuous extrudate is supported horizontally in a single plane as the process proceeds up until the cutting of segments thereof by a cutter located downstream of the second puller. Since the heating and cooling times of the continuous extrusion are dependent on its cross-sectional shape, certain minimum times in each process stage must be adhered to so that the core of the cross-section reaches the required temperature. The combined time for the entire process coupled with the process rate of between 0.4 and 2 feet per minute require a production line of about 50 feet or even longer.